Highly ordered and uniformly porous structure of conductive foams is a vital issue for various functional purposes such as piezoresistive sensing and electromagnetic interference (EMI) shielding. With the aids of Kevlar polyanionic chains, thermoplastic polyurethane (TPU) foams reinforced by aramid nanofibers (ANF) with adjustable pore-size distribution were successfully obtained via a non-solvent-induced phase separation. In this regard, the most outstanding result is the in situ formation of ANF in TPU foams after protonation of Kevlar polyanion during the NIPS process. Furthermore, in situ growth of copper nanoparticles (Cu NPs) on TPU/ANF foams was performed according to the electroless deposition by using the tiny amount of pre-blended Ti3C2Tx MXene as reducing agents. Particularly, the existence of Cu NPs layers significantly promoted the storage modulus in 2,932% increments, and the well-designed TPU/ANF/Ti3C2Tx MXene (PAM-Cu) composite foams showed distinguished compressive cycle stability. Taking virtues of the highly ordered and elastic porous architectures, the PAM-Cu foams were utilized as piezoresistive sensor exhibiting board compressive interval of 0-344.5 kPa (50% strain) with good sensitivity at 0.46 kPa-1. Meanwhile, the PAM-Cu foams displayed remarkable EMI shielding effectiveness at 79.09 dB in X band. This work provides an ideal strategy to fabricate highly ordered TPU foams with outstanding elastic recovery and excellent EMI shielding performance, which can be used as a promising candidate in integration of satisfactory piezoresistive sensor and EMI shielding applications for human-machine interfaces. 

/pdf/highly-ordered-thermoplastic-polyurethane-aramid-nanofiber-1zfpkp6r.pdf

Highly Ordered Thermoplastic Polyurethane/Aramid Nanofiber Conductive Foams Modulated by Kevlar Polyanion for Piezoresistive Sensing and Electromagnetic Interference Shielding

Diabetic wound is one of the common complications in diabetic patients, which exhibits chronic, hard-to-heal characteristics. The healing process of wounds is impaired by several factors, including excessive oxidative stress, blocked angiogenesis, and bacterial infection. The therapeutic effects of traditional microneedle patches remain not satisfactory, due to their difficulty simultaneously targeting multiple targets to treat diabetic wounds. As such, there is an urgent need to develop a multifunctional microneedle (MN) patch for promoting the healing of diabetic wounds. A multifunctional MN patch with antioxidant, proangiogenesis, and antibacterial capacities was fabricated to target the pathogenesis of diabetic wounds. Silk fibroin methacryloyl, which has excellent biocompatibility, stable mechanical properties, and well processability, and is selected as the base material for multifunctional MN patches. Prussian blue nanozymes (PBNs) and vascular endothelial growth factor (VEGF) are encapsulated in tips of MN patches, Polymyxin is encapsulated in base layers of MN patches. Based on synergic properties of these components, multifunctional MN patches exhibit excellent biocompatibility, drug-sustained release, proangiogenesis, antioxidant, and antibacterial properties. The developed multifunctional MN patches accelerate diabetic wound healing, providing a potential therapeutic approach.

Multifunctional Silk Fibroin Methacryloyl Microneedle for Diabetic Wound Healing.

Organoids, miniature and simplified in vitro model systems that mimic the structure and function of organs, have attracted considerable interest due to their promising applications in disease modeling, drug screening, personalized medicine, and tissue engineering. Despite the substantial success in cultivating physiologically relevant organoids, challenges remain concerning the complexities of their assembly and the difficulties associated with data analysis. The advent of AI-Enabled Organoids, which interfaces with artificial intelligence (AI), holds the potential to revolutionize the field by offering novel insights and methodologies that can expedite the development and clinical application of organoids. This review succinctly delineates the fundamental concepts and mechanisms underlying AI-Enabled Organoids, summarizing the prospective applications on rapid screening of construction strategies, cost-effective extraction of multiscale image features, streamlined analysis of multi-omics data, and precise preclinical evaluation and application. We also explore the challenges and limitations of interfacing organoids with AI, and discuss the future direction of the field. Taken together, the AI-Enabled Organoids hold significant promise for advancing our understanding of organ development and disease progression, ultimately laying the groundwork for clinical application. 

AI-enabled organoids: Construction, analysis, and application

Recent approaches for enhancing the performance of dissolving microneedles in drug delivery applications

Transdermal delivery provides numerous benefits over conventional routes of administration. However, this strategy is generally limited to a few molecules with specific physicochemical properties (low molecular weight, high potency, and moderate lipophilicity) due to the barrier function of the stratum corneum layer. Researchers have developed several physical enhancement techniques to expand the applications of the transdermal field; among these, microneedle technology has recently emerged as a promising platform to deliver therapeutic agents of any size into and across the skin. Typically, hydrophilic biomolecules cannot penetrate the skin by passive diffusion. Microneedle insertion disrupts skin integrity and compromises its protective function, thus creating pathways (microchannels) for enhanced permeation of macromolecules. Microneedles not only improve stability but also enhance skin delivery of various biomolecules. Academic institutions and industrial companies have invested substantial resources in the development of microneedle systems for biopharmaceutical delivery. This review article summarizes the most recent research to provide a comprehensive discussion about microneedle-mediated delivery of macromolecules, covering various topics from the introduction of the skin, transdermal delivery, microneedles, and biopharmaceuticals (current status, conventional administration, and stability issues), to different microneedle types, clinical trials, safety and acceptability of microneedles, manufacturing and regulatory issues, and the future of microneedle technology.

/pdf/microneedle-mediated-transdermal-delivery-of-3fzm5ybp.pdf

Microneedle-Mediated Transdermal Delivery of Biopharmaceuticals

The ever-increasing threats of multidrug-resistant bacteria and their biofilm-associated infections have bred a desperate demand for alternative remedies to combat them. Near-infrared (NIR)-absorbing photothermal agent (PTAs)-mediated photothermal therapy (PTT) is particularly attractive for biofilm ablation thanks to its superiorities of noninvasive intervention, satisfactory antibacterial efficiency, and less likelihood to develop resistance. Herein, three butterfly-shaped aggregation-induced emission luminogens (AIEgens) with balanced nonradiative decay (for conducting PTT) and radiative decay (for supplying fluorescence in the NIR-II optical window) are rationally designed for imaging-assisted photothermal obliteration of bacterial biofilms. After being encapsulated into cationic liposomes, AIEgens-fabricated nanoparticles can eradicate a wide spectrum of biofilms formed by Gram-positive bacteria (methicillin-resistant Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) upon an 808 nm laser irradiation. In vivo experiments firmly demonstrate that the NIR-II AIE liposomes with excellent biocompatibility perform well in both the P. aeruginosa biofilm-induced keratitis mouse model and the MSRA biofilm-induced skin infection mouse model.

Adding Flying Wings: Butterfly-Shaped NIR-II AIEgens with Multiple Molecular Rotors for Photothermal Combating of Bacterial Biofilms.

A coating of implanted medical devices with antifouling ability, preferable mechanical property and stability in the physiological environment proves beneficial for their clinical use. Here we develop a flexible bilayer hydrogel coating with self-healing, antifouling, and lubricating functions. Our bilayer coating consists of two functional layers: i) an adhesive flexible polyelectrolyte hydrogel layer, ii) an antifouling and lubricous polyzwitterionic layer. The bilayer hydrogel coating is prepared in two steps dip-coating and in situ UV photopolymerization. Our results demonstrate that the prepared bilayer hydrogel coating has proper mechanical properties, favorable hydrophilicity, and lower surface friction. We demonstrate that the bilayer hydrogel coating maintains hydrophilicity under extreme condition (1 h sonicating or 5000 times repeating bending). The as-prepared bilayer hydrogel coating resists non-specific protein adsorption, inhibits cell and platelet adhesion, and prevents thrombosis. This work provides a reliable coating on the medical materials, showing a promising practical application in diversified implantable medical devices. 

A polyzwitterion-based antifouling and flexible bilayer hydrogel coating

Vascular restenosis after balloon dilation is largely caused by the over-proliferation of smooth muscle cells, which is triggered and exacerbated by local excessive inflammation and oxidative stress. The excessive inflammatory and oxidative stress cause tissue/cell damage, hamper endothelial functions, and worsen intimal hyperplasia and restenosis. A high level of reactive oxygen species (ROS) overproduction is regarded as the main culprit. Therefore, efficiently inhibiting ROS over-production or weightily depleting them is of great significance. Herein, a “ROS-responsive/scavenging prodrug” is introduced into balloon coating for the treatment of vascular restenosis. A reversible phenylboronic ester-bearing caffeic acid (CA) macromolecular prodrug (PBC) is designed for the controlled and on-demand dual-drug release triggered by the local high ROS level; the released CA and 4-hydroxybenzyl alcohol exhibit efficient antioxidant and anti-inflammatory effects by scavenging ROS, thereby regulating vascular microenvironment and protecting endothelium functions. To accelerate endothelium regeneration, pro-endothelial microRNA-126 is further introduced. The ROS-responsive/scavenging prodrug/miRNA balloon coating efficiently prevents intimal hyperplasia, alleviates local inflammation, and improves endothelium healing in a rat abdominal aorta restenosis model, which may provide applicative perspectives for next-generation drug-coated balloons and other cardiovascular diseases treatment. 

Precise Regulation of Inflammation and Oxidative Stress by ROS‐Responsive Prodrug Coated Balloon for Preventing Vascular Restenosis

Infected wound healing is a complex and dynamic process affecting millions of people. Since wound healing contains multiple stages, it requires staged management to realize the early inhibition of infection and the subsequent promotion of wound healing. A key point is to design a biphasic release system with antibacterial agents and growth factors to promote wound regeneration. As a safe, efficient and painless transdermal drug delivery method, microneedles (MNs) have attracted widespread attention. Herein, we present dissolving MNs with the biphasic release of an antibacterial agent and a growth factor to promote wound healing. bFGF was first encapsulated in PLGA microspheres (bFGF@PLGA) and then co-loaded with free ofloxacin onto polyvinylpyrrolidone MNs. Owing to the fast dissolution of the substrate, ofloxacin was quickly released to rapidly inhibit infection, while the PLGA microspheres were left in the wound. Due to the slow degradation of PLGA, bFGF encapsulated in the PLGA microspheres was slowly released to further promote wound healing. In vivo studies demonstrated that the MNs with the biphasic release of antibacterial agent and growth factor exhibited a superior capability to promote wound healing. This biphasic release system combined with microneedles has a bright future in wound healing.

Dissolving microneedles with a biphasic release of antibacterial agent and growth factor to promote wound healing.

No effective therapeutic dressings are currently available in the market that can prevent bacterial infection and simultaneously promote skin regeneration in diabetic patients. The lack of re-epithelization, prevalence of inflammation, and high risk of infection are hallmarks of non-healing wounds. Here, we have evaluated the antimicrobial and pro-regenerative effect of a relatively non-leaching LL37 peptide immobilized in polyurethane (PU)-based wound dressings (PU-adhesive-LL37 dressing). The PU-adhesive-LL37 (63 μg LL37NPs/cm2) dressing killed Gram-positive and Gram-negative bacteria in human serum without inducing bacterial resistance after 16 antimicrobial test cycles in contrast to commercially available dressings with the capacity to release antimicrobial Ag ions. Importantly, type II diabetic mice (db/db mice) treated with the PU-adhesive-LL37 dressing for different periods of time (6 or 14 days) showed enhanced wound healing and re-epithelialization (i.e., high keratin 14/5 levels) and lower macrophage infiltration in the wounds compared to animals treated with PU. The wounds treated with PU-adhesive-LL37 dressings showed also low expression of pro-inflammatory cytokines such as TNF-α and IL6 after 6 days of treatment, indicating that they act as an anti-inflammatory dressing. Additionally, PU-adhesive-LL37 dressings do not induce acute inflammatory responses in the peripheral blood mononuclear cells (PBMCs) after 3 days of exposure, in contrast to controls. Taken together, PU-adhesive-LL37NP dressings might prevent the bacterial infections and facilitate wound healing by tissue contact, inducing re-epithelialization and anti-inflammatory processes in diabetic conditions.

Antimicrobial Peptide-Tether Dressing Able to Enhance Wound Healing by Tissue Contact.

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